Q9UBR1 · BUP1_HUMAN
- ProteinBeta-ureidopropionase
- GeneUPB1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids384 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes a late step in pyrimidine degradation (PubMed:22525402, PubMed:24526388).
Converts N-carbamoyl-beta-alanine (3-ureidopropanoate) into beta-alanine, ammonia and carbon dioxide (PubMed:10415095, PubMed:10542323, PubMed:11508704, PubMed:22525402, PubMed:24526388, PubMed:29976570).
Likewise, converts N-carbamoyl-beta-aminoisobutyrate (3-ureidoisobutyrate) into beta-aminoisobutyrate, ammonia and carbon dioxide (Probable)
Converts N-carbamoyl-beta-alanine (3-ureidopropanoate) into beta-alanine, ammonia and carbon dioxide (PubMed:10415095, PubMed:10542323, PubMed:11508704, PubMed:22525402, PubMed:24526388, PubMed:29976570).
Likewise, converts N-carbamoyl-beta-aminoisobutyrate (3-ureidoisobutyrate) into beta-aminoisobutyrate, ammonia and carbon dioxide (Probable)
Catalytic activity
- 3-(carbamoylamino)propanoate + 2 H+ + H2O = beta-alanine + CO2 + NH4+This reaction proceeds in the forward direction.
Activity regulation
Strongly inhibited by 50 mM Zn2+. Not inhibited by EDTA. Competitively inhibited by beta-alanine, 5-aminolevulinic acid (ALA), beta-aminoisobutyrate and 4-ureidobutyrate.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
15.5 μM | N-carbamoyl-beta-alanine | |||||
48 μM | N-carbamoyl-beta-alanine |
kcat is 0.47 sec-1 with N-carbamoyl-beta-alanine as substrate.
pH Dependence
Optimum pH is 6.5.
Pathway
Amino-acid biosynthesis; beta-alanine biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 119 | Proton acceptor | ||||
Sequence: E | ||||||
Active site | 196 | Proton donor | ||||
Sequence: K | ||||||
Active site | 233 | Nucleophile | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Molecular Function | beta-ureidopropionase activity | |
Molecular Function | protein homodimerization activity | |
Biological Process | beta-alanine biosynthetic process via 3-ureidopropionate | |
Biological Process | CMP catabolic process | |
Biological Process | dCMP catabolic process | |
Biological Process | dUMP catabolic process | |
Biological Process | in utero embryonic development | |
Biological Process | liver development | |
Biological Process | protein homooligomerization | |
Biological Process | protein homotetramerization | |
Biological Process | pyrimidine nucleoside catabolic process | |
Biological Process | UMP catabolic process |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBeta-ureidopropionase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9UBR1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Beta-ureidopropionase deficiency (UPB1D)
- Note
- DescriptionAn inborn error of metabolism due to a defect in pyrimidine degradation. It is characterized by muscular hypotonia, dystonic movements, scoliosis, microcephaly and severe developmental delay. Patients show strongly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in plasma, cerebrospinal fluid and urine.
- See alsoMIM:613161
Natural variants in UPB1D
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_081207 | 13 | L>S | in UPB1D; strongly reduced activity; reduced formation of higher oligomers; dbSNP:rs200688546 | |
VAR_026752 | 85 | A>E | in UPB1D; complete loss of activity; dbSNP:rs34035085 | |
VAR_081208 | 235 | G>R | in UPB1D; complete loss of activity; dbSNP:rs766196011 | |
VAR_081209 | 236 | R>W | in UPB1D; complete loss of activity; dbSNP:rs144135211 | |
VAR_081210 | 264 | S>R | in UPB1D; complete loss of activity | |
VAR_081211 | 271 | E>K | in UPB1D; complete loss of activity; abolishes formation of higher oligomers; dbSNP:rs747454154 | |
VAR_081212 | 286 | I>T | in UPB1D; uncertain significance; mildly reduced enzyme activity; no effect on formation of higher oligomers; dbSNP:rs200034079 | |
VAR_081213 | 326 | R>Q | in UPB1D; complete loss of activity; abolishes formation of higher oligomers; dbSNP:rs118163237 | |
VAR_081214 | 359 | T>M | in UPB1D; complete loss of activity; dbSNP:rs369879221 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_081207 | 13 | in UPB1D; strongly reduced activity; reduced formation of higher oligomers; dbSNP:rs200688546 | |||
Sequence: L → S | ||||||
Natural variant | VAR_026752 | 85 | in UPB1D; complete loss of activity; dbSNP:rs34035085 | |||
Sequence: A → E | ||||||
Mutagenesis | 130 | Loss of catalytic activity. | ||||
Sequence: R → I | ||||||
Mutagenesis | 132 | Loss of catalytic activity. Forms dimers, but no higher oligomers. | ||||
Sequence: K → L | ||||||
Mutagenesis | 208 | Loss of catalytic activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 208 | Loss of catalytic activity. Forms dimers, but no higher oligomers. | ||||
Sequence: S → C | ||||||
Mutagenesis | 208 | Loss of catalytic activity. Forms dimers, but no higher oligomers. | ||||
Sequence: S → R | ||||||
Mutagenesis | 233 | Loss of catalytic activity. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_081208 | 235 | in UPB1D; complete loss of activity; dbSNP:rs766196011 | |||
Sequence: G → R | ||||||
Natural variant | VAR_081209 | 236 | in UPB1D; complete loss of activity; dbSNP:rs144135211 | |||
Sequence: R → W | ||||||
Natural variant | VAR_081210 | 264 | in UPB1D; complete loss of activity | |||
Sequence: S → R | ||||||
Natural variant | VAR_081211 | 271 | in UPB1D; complete loss of activity; abolishes formation of higher oligomers; dbSNP:rs747454154 | |||
Sequence: E → K | ||||||
Natural variant | VAR_081212 | 286 | in UPB1D; uncertain significance; mildly reduced enzyme activity; no effect on formation of higher oligomers; dbSNP:rs200034079 | |||
Sequence: I → T | ||||||
Mutagenesis | 299 | Loss of catalytic activity. Forms dimers, but no higher oligomers. | ||||
Sequence: T → C | ||||||
Natural variant | VAR_081213 | 326 | in UPB1D; complete loss of activity; abolishes formation of higher oligomers; dbSNP:rs118163237 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_050280 | 340 | in dbSNP:rs34110964 | |||
Sequence: A → D | ||||||
Natural variant | VAR_081214 | 359 | in UPB1D; complete loss of activity; dbSNP:rs369879221 | |||
Sequence: T → M |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 518 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000204051 | 1-384 | Beta-ureidopropionase | |||
Sequence: MAGAEWKSLEECLEKHLPLPDLQEVKRVLYGKELRKLDLPREAFEAASREDFELQGYAFEAAEEQLRRPRIVHVGLVQNRIPLPANAPVAEQVSALHRRIKAIVEVAAMCGVNIICFQEAWTMPFAFCTREKLPWTEFAESAEDGPTTRFCQKLAKNHDMVVVSPILERDSEHGDVLWNTAVVISNSGAVLGKTRKNHIPRVGDFNESTYYMEGNLGHPVFQTQFGRIAVNICYGRHHPLNWLMYSINGAEIIFNPSATIGALSESLWPIEARNAAIANHCFTCAINRVGTEHFPNEFTSGDGKKAHQDFGYFYGSSYVAAPDSSRTPGLSRSRDGLLVAKLDLNLCQQVNDVWNFKMTGRYEMYARELAEAVKSNYSPTIVKE | ||||||
Modified residue | 378 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in liver (at protein level).
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 72-344 | CN hydrolase | ||||
Sequence: VHVGLVQNRIPLPANAPVAEQVSALHRRIKAIVEVAAMCGVNIICFQEAWTMPFAFCTREKLPWTEFAESAEDGPTTRFCQKLAKNHDMVVVSPILERDSEHGDVLWNTAVVISNSGAVLGKTRKNHIPRVGDFNESTYYMEGNLGHPVFQTQFGRIAVNICYGRHHPLNWLMYSINGAEIIFNPSATIGALSESLWPIEARNAAIANHCFTCAINRVGTEHFPNEFTSGDGKKAHQDFGYFYGSSYVAAPDSSRTPGLSRSRDGLLVAKLDL |
Sequence similarities
Belongs to the carbon-nitrogen hydrolase superfamily. BUP family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length384
- Mass (Da)43,166
- Last updated2000-05-01 v1
- Checksum62B81982D2D63CC3
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 263 | in Ref. 1; AAF06739 | ||||
Sequence: L → LRSL |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF163312 EMBL· GenBank· DDBJ | AAF06735.1 EMBL· GenBank· DDBJ | mRNA | ||
AF169559 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169550 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169551 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169552 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169553 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169554 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169555 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169556 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169557 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF169558 EMBL· GenBank· DDBJ | AAF06739.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB013885 EMBL· GenBank· DDBJ | BAA88634.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456375 EMBL· GenBank· DDBJ | CAG30261.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471095 EMBL· GenBank· DDBJ | EAW59663.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC131703 EMBL· GenBank· DDBJ | AAI31704.1 EMBL· GenBank· DDBJ | mRNA |